SARS coronavirus: a new challenge for prevention and therapy.
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ABSTRACT:
SUBMITTER: Holmes KV
PROVIDER: S-EPMC156116 | biostudies-literature | 2003 Jun
REPOSITORIES: biostudies-literature
Publications
SARS coronavirus: a new challenge for prevention and therapy.
The Journal of clinical investigation 20030601 11
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Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection
2010-06-05 | E-GEOD-546 | biostudies-arrayexpress
Project description:OBJECTIVES:Following the public-health emergency of international concern (PHEIC) declared by the World Health Organization (WHO) on 30 January 2020 and the recent outbreak caused by 2019 novel coronavirus (2019-nCoV) [officially renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] in China and 29 other countries, we aimed to summarise the clinical aspects of the novelBetacoronavirus disease (COVID-19) and its possible clinical presentations together with suggested therapeutic algorithms for patients who may require antimicrobial treatment. METHODS:The currently available literature was reviewed for microbiologically confirmed infections by 2019-nCoV or COVID-19 at the time of writing (13 February 2020). A literature search was performed using the PubMed database and Cochrane Library. Search terms included 'novel coronavirus' or '2019-nCoV' or 'COVID-19'. RESULTS:Published cases occurred mostly in males (age range, 8-92 years). Cardiovascular, digestive and endocrine system diseases were commonly reported, except previous chronic pulmonary diseases [e.g. chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis] that were surprisingly underreported. Fever was present in all of the case series available, flanked by cough, dyspnoea, myalgia and fatigue. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral ground-glass opacities were the main reported radiological features of 2019-nCoV infection, at least in the early phases of the disease. CONCLUSION:The new 2019-nCoV epidemic is mainly associated with respiratory disease and few extrapulmonary signs. However, there is a low rate of associated pre-existing respiratory co-morbidities.
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Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection Keywords: repeat sample
2003-10-19 | GSE546 | GEO
Project description:SARS-coronavirus-2 (SARS-CoV-2), the etiologic agent of the new lung disease COVID-19 is closely related to SARS-CoV, and together with MERS-CoV are three new human coronaviruses that emerged in the last 20 years. The COVID-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with SARS and MERS. Clinical presentations range from asymptomatic or mild symptoms to severe illness. The prevalent cause of mortality is pneumonia that progresses to ARDS. The ongoing pandemic has already resulted in more than 135,000 deaths and an unprecedented burden on national health systems worldwide. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Trials are based on repurposed drugs that are already approved for other infections, have acceptable safety profiles or have performed well in animal studies against the other two deadly coronaviruses. Supportive care remains the mainstay of therapy at present, as it is still unclear how well these data can be extrapolated to SARS-CoV-2. Most of those emerging re-introduced drugs are administered to patients in the context of clinical trials. In this review, we summarize the strategies currently employed in the treatment of COVID-19.
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Project description:Severe pneumonia by the novel coronavirus (COVID-19 infection) is mediated through immune dysregulation. It was studied if this dysregulation persists after recovery and if it is linked to the manifestation of post-covid syndrome (PCS). Patients who had been hospitalized for COVID-19 pneumonia 3 to 6 months ago during two different time periods and matched comparators were the derivation cohort (n=46, September-October 2020) and the validation cohort (n=484, April-July 2021) respectively. Peripheral blood mononuclear cells (PBMCs) were isolated for culture and cytokine stimulation. Patients provided answers to two health questionnaires allowing classification into PCS and were also subject to lung function tests (LFT). The primary endpoint was the modulation of the production of interleukin (IL)-1b and IL-6 from monocytes and among secondary, the modulation of adaptive immune response and the development of PCS. Increased production of IL-1b (p<0.001) and IL-6 (p<0.001) was found in both study periods compared to control. There was increase of pro-inflammatory Th1 responses over anti-inflammatory Th2 responses and attenuation of the T17 response. PCS was manifested in 22% of patients, grouped into three groups of symptoms. Fatigue was associated with the predominance of Th2 responses and abnormal LFT with overproduction of IL-1b and IL-6. Immune dysregulation is apparent after three months post COVID-19 pneumonia with main features the hyper-production of IL-1β and IL-6 by circulating monocytes, the increase of the Th1/Th2 ratio and the attenuation of T17 response.
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Project description:The new corona virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) causes a disease called COVID-19 (coronavirus disease 2019), that develops mostly in subjects with already impaired immune system function, primarily in the elderly and in individuals with some chronic disease or condition. The reasons for this should be sought in the processes of aging and chronic latent inflammation, i.e. immunosenescence and inflammaging. Laboratory medicine specialists are currently focused on proving the presence of the virus and defining biomarkers that would enable the prediction of disease progression. For now, it has been shown that useful biomarkers can include general biomarkers of inflammation (parameters of complete blood count, C-reactive protein, interleukin-6, procalcitonin), biomarkers of myocardial damage (high sensitivity troponin I/T, B-type natriuretic peptide, and N-terminal B type natriuretic peptide), and vascular biomarkers (D-dimer, prothrombin time, fibrinogen). Their actual diagnostic specificity, sensitivity and predictive value need to be tested on a larger number of subjects. In addition, it is important to find and evaluate specific biomarkers of immunosenescence.
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Project description:SARS coronavirus main protease (SARS-CoV M(pro)) is essential for the replication of the virus and regarded as a major antiviral drug target. The enzyme is a cysteine protease, with a catalytic dyad (Cys-145/His-41) in the active site. Aldehyde inhibitors can bind reversibly to the active-site sulfhydryl of SARS-CoV M(pro). Previous studies using peptidic substrates and inhibitors showed that the substrate specificity of SARS-CoV M(pro) requires glutamine in the P1 position and a large hydrophobic residue in the P2 position. We determined four crystal structures of SARS-CoV M(pro) in complex with pentapeptide aldehydes (Ac-ESTLQ-H, Ac-NSFSQ-H, Ac-DSFDQ-H, and Ac-NSTSQ-H). Kinetic data showed that all of these aldehydes exhibit inhibitory activity towards SARS-CoV M(pro), with K(i) values in the ?M range. Surprisingly, the X-ray structures revealed that the hydrophobic S2 pocket of the enzyme can accommodate serine and even aspartic-acid side-chains in the P2 positions of the inhibitors. Consequently, we reassessed the substrate specificity of the enzyme by testing the cleavage of 20 different tetradecapeptide substrates with varying amino-acid residues in the P2 position. The cleavage efficiency for the substrate with serine in the P2 position was 160-times lower than that for the original substrate (P2=Leu); furthermore, the substrate with aspartic acid in the P2 position was not cleaved at all. We also determined a crystal structure of SARS-CoV M(pro) in complex with aldehyde Cm-FF-H, which has its P1-phenylalanine residue bound to the relatively hydrophilic S1 pocket of the enzyme and yet exhibits a high inhibitory activity against SARS-CoV M(pro), with K(i)=2.24±0.58 ?M. These results show that the stringent substrate specificity of the SARS-CoV M(pro) with respect to the P1 and P2 positions can be overruled by the highly electrophilic character of the aldehyde warhead, thereby constituting a deviation from the dogma that peptidic inhibitors need to correspond to the observed cleavage specificity of the target protease.
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